Corrective surgery alters plasma protein profiling in congenital heart diseases and clinical perspectives

The final goal for treatment of congenital heart diseases (CHD) is to resume not only the normal heart structure but also physiology. The present study evaluates surgical results at molecular basis on the proteomic pattern in the pre- and post-operative period in tetralogy of Fallot (TOF) and ventricular septal defect (VSD) in order to find whether structure repair is associated with clinically important molecular changes in CHD. Differential protein analysis by using two-dimensional gel electrophoresis and mass spectrometry followed by ELISA validation was performed in the plasma samples of patients with TOF (n=82) or VSD (n=82) preoperatively, 6-month postoperatively, and in normal controls (n=82). A total of 473 protein spots in preoperative patients and 515 in postoperative patients were detected. Significantly (P<0.01) downregulated or upregulated proteins were detected. Validation of proteins in the new cohort of patients demonstrated that in VSD patients, postoperative complement component C3c (P<0.05) was partially and serum amyloid P-component (P<0.05) was completely recovered. In TOF patients, postoperative gelsolin (P<0.05) was partially recovered. In contrast, the elevated fibrinogen gamma chain level (P<0.01) in preoperative patients became normal postoperatively (P=0.1 vs. control). Thus, we have for the first time by using proteomic methods demonstrated that repair surgery for CHD not only corrects the structure malformation but also resumes the normality of certain altered proteins at molecular level. Identification of the recovered or unchanged proteins may facilitate the evaluation of the surgical results and the personalized management in postoperative period and long-term.